Targeting HMGB1 in the Treatment of Non-Small Cell Lung Adenocarcinoma

Abstract

Evidence of immunogenic cell death as a predictor of response to cancer therapy has increased interest in the high molecular group box 1 protein (HMGB1). HMGB1 is a nuclear protein associated with chromatin organization and DNA damage repair. HMGB1 is also a damage-associated molecular pattern (DAMP) protein and promotes proinflammatory signaling in a paracrine and autocrine manner. Extracellular HMGB1 can promote activation of NF-kB and is associated with several chronic inflammatory and autoimmune diseases, including sepsis, rheumatoid arthritis, atherosclerosis, chronic kidney disease, systemic lupus erythematosus (SLE), as well as cancer. In this review, we describe studies that demonstrate the use of deacetylase inhibitors and HMGB1 inhibitors to alter the expression and localization of HMGB1 in cancer cells, with a focus on lung cancer. The drugs described herein are well established and frequently used in human and small mammal studies. The main objective of this review is to summarize the potential benefit of targeting posttranslational modification of HMGB1 to decrease inflammatory signaling in the tumor microenvironment, and perhaps lead to improved response to current immunotherapeutic approaches.

Role of Extracellular High-Mobility Group Box-1 as a Therapeutic Target of Gastric Cancer

“…Intracellular HMGB1 is released extracellularly from immune cells during inflammation or from tumor cells due to cytotoxicity, stress, necrosis, and autophagy [ 43 , 44 , 45 ]. Inflammation, including tumor-related inflammation, is the main factor contributing to the release of HMGB1; however, the release of HMGB1 from tumor cells themselves may also contribute to the high plasma concentration of HMGB1 in the tumor-bearing state [ 21 ].…”